Project summary The long-term objective of this program of research is to further our understanding of the brain mechanisms associated with the selection, preparation and execution of motor responses. The better we understand these mechanisms the better we can translate this knowledge into useful real-world applications such as, for example, brain-machine interfaces. Most of the current brain-machine application studies are based on the knowledge that movement parameters such as movement direction and speed are important factors determining the activity of neurons in motor-related areas. The classical paradigm used to investigate the relation between neuronal activity and movement parameters has been the center-out task in which hand movements are made from a starting position toward one of several equiprobable and unambiguous targets. Although, this methodology has provided a great deal of important findings it does not take into account that in the real world motor responses are rarely selected among a set of equally probable responses and that the selection of the response is not always evident. On the contrary, efficient planning and control of movements depends greatly on the knowledge that some motor responses are more likely than others, and on the capacity to quickly process the information that is relevant. For example, a hunter may be able to predict to some extent the upcoming direction of a deer from cracklings in the woods, for example. However, it is also important that the target be recognized as a deer before shooting. For these reasons, it is important to extend the investigations of how the brain plans and controls movements in more complex conditions than those that have been used so far. To this end, we plan to investigate the preparation of reaching movements in different conditions of predictability of target direction and in different conditions of target ambiguity. Te research strategy is to study human and non-human primate subjects in the same tasks to provide a basis of comparison of behavior and neural processes between the two species. The neural processes of motor preparation and response selection will be investigated using single unit activity as well as local field potentials in the motor cortex of non-human primates, and magnetoencephallography in human subjects. Understanding how these signals reflect motor preparation and response selection in contexts of uncertainty and ambiguity is highly relevant to the development of brain-machine interfaces.